Serum glucose level-dependent and independent modulation of mu-opioid agonist-mediated analgesia in diabetic mice.

We examined the effect of insulin on the analgesic potency of DAMGO, a selective agonist of mu-opioid receptors, in mice which had been rendered diabetic by an injection of streptozotocin (STZ; 200 mg/kg, i.v.) 1 and 2 weeks previously. The analgesic potency of DAMGO, based on the tail-flick test, was significantly decreased in both the 1 and 2-week diabetic mice as compared to its effect in age-matched controls. Sensitivity to the analgesic potency of DAMGO returned to normal when insulin was administered to STZ-induced 1-week diabetic mice. However, pretreatment with insulin had no significant effect on the sensitivity to the analgesic potency of DAMGO in 2-week diabetic mice. These results suggest that the serum glucose levels may possibly be responsible for the altered potency of mu-opioid agonists only during the incipient stages of diabetes.